Well-Defined Macromolecule-Magnetic Nanoparticle Complexes

研究计划的智力价值。 本研究的重点是嵌段共聚物的分子设计与锚段预期绑定到磁性金属或金属氧化物颗粒和尾部块，以提供空间位阻在水性和有机载体介质。 重点是致力于两个相互关联的推力。 一个包括合成的共聚物分散剂与疏水性，玻璃态锚块和控制分子量的尾巴，作为胶束模板生成控制尺寸的钴纳米粒子的功能的研究，分散性能相关的粒径和共聚物的结构/形态，和分析它们在提高磁性金属纳米粒子的耐久性的有效性。 第二个推力包括磁铁矿的酶促降解分散剂的设计，以及随着其直径从10纳米增加到100纳米，与磁性尺寸相关的磁粒的研究。 这些分散剂具有硅烷或硅氧烷锚，其具有羧酸酯结合基团和选择的肽尾嵌段。 多肽嵌段包括具有基本上单峰分子量分布的模型，与通过马来酰亚胺活化的氨基酸偶联或通过N-羧基氰基丙烯酸酯开环在容易的聚合中制备的那些相比。研究的预期成果是制备尺寸可控的钴和磁性纳米颗粒的方法，以及用大分子分散剂包覆。 所获得的有关共聚物结构和组成、粒度和粒径的知识将使复合物能够以尽可能高的磁性组分体积分数制备。 这将提供具有最高磁响应的可分散磁性复合物。 它也将提供一个坚实的基础，预测其他粒子-高分子组合物的性能，作为未来的无机磁性元件的开发。 该计划的预期更广泛的方面：定制的大分子与磁性金属和金属氧化物纳米颗粒的复合物可以为微电子和关键的生物医学技术“打开大门”。 生物学应用包括动脉内、磁场导向的药物定位、用于骨髓治疗的磁分离的细胞靶向、用于通过交变磁场产生的热治疗难以到达的恶性肿瘤的局部体内高热治疗、改进的诊断成像工具和视网膜脱离的治疗的可能性。 定制的大分子分散剂的开发和理解是获得在复合物中具有最大体积分数的磁性组分的材料的关键，所述复合物保持可分散在必要的载体介质中。 还可能的是：（1）用于合成这些纳米颗粒的反应介质的溶液结构可用于控制原位生成的粒度，（2）改进的聚合物涂层可赋予生物相容性，以及（3）这些涂层可改进颗粒抗氧化的耐久性。 该计划将集中于培养研究生。 在这方面，人们认识到，今天的基础研究方法是多学科和全球性的。 学生将通过完成1-cr课程，在整个课程中就相互关联的研究课题进行合作，从而提高所需的团队建设和沟通技能。在技术写作和技术口头交流方面，每年参加科学会议，介绍研究成果。 他们将参加一个国际多学科工作组，通过电子方式分享想法，并为小组中的物理学家和药理学家准备研究模型材料。 通过这种方式，他们将获得与其材料相关的多学科研究成果，并将有助于建立研究基础设施，使物理学家和药理学家能够对定义明确的大分子和大分子-磁性颗粒复合物进行仔细研究。

Intellectual Merit of the Research Program. This research focuses on the molecular design of block copolymers with anchor segments expected to bind to magnetic metal or metal oxide particles and tail blocks to provide steric dispersibility in aqueous and organic carrier media. Emphasis is devoted to two inter-related thrusts. One includes syntheses of copolymer dispersants with hydrophobic, glassy anchor blocks and controlled molecular weight tails, a study of their function as micellar templates for generating controlled-size cobalt nanoparticles, dispersive properties as related to particle size and copolymer structure/morphology, and anaylses of their effectiveness in improving durability of magnetic metal nanoparticles. The second thrust encompasses the design of enzymatically degradable dispersants for magnetite, and a study of dispersibility as related to magnetic size as it is increased from 10-100 nm in diameter. These dispersants have silane or siloxane anchors with carboxylate binding groups and selected peptide tail blocks. The polypeptide blocks include models with essentially uni-modal molecular weight distributions as compared to those prepared in facile polymerizations via carbodiimide-activated aminoacid coupling or by ring-opening of N-carboxyanhydrides. Anticipated outcomes of teh research are methodologies for preparing controlled size cobalt and magnetic nanoparticles, well-coated with macromolecular dispersants. The knowledge gained relating copolymer structure and composition, particle size, and dispersibility will enable complexes to be prepared with the highest possible volume fractions of the magnetic components. This will provide dispersible magnetic complexes with the highetst magnetic response. It will also provide a firm basis for predicting properties of other particle-macromolecular compositions as future inorganic magnetic components are developed. Anticipated Broader Aspects of the Program: Complexes of tailored macromolecules with magnetic metal and metal oxide nanoparticles could "open the door" to microelectronics and critical biomedical technologies. Biological applicatons include possibilities for intra-arterial, magnetic field-directed localization of drugs, cell targeting with magnetic separations for bone marrow treatments, localized in-vivo hyperthermia treatments for treating difficult-to-reach malignancies with heat generated via alternating magnetic fields, improved diagnostic imaging tools, and treatments for retinal detachments. The development and understanding of tailored macromolecular dispersants hold the key to obtaining materials with the maximum volume fraction of the magnetic component in the complexes that remain dispersible in the necessary carrier media. It is also probable (1) that the solution structures of the reaction media for synthesizing these nanoparticles can be used to control the in-situ generated particle size, (2) that improved polymer coatings can impart biocompatibility, and (3) that these coatings can improve particle durability against oxidation. The program will concentrate on educating graduate students. In this vein, it is recognized that today's fundamental research methods are multi-disciplinary and global. The students will enhance needed team-building and communication skills by collaborating throughout the program on inter-related research thrusts, by completing a 1-cr. course each in technical writing and in technical oral communication, and by annual participation in scientific meetings to present research findings. They will participate in an international multi-disciplinary working group by electronically sharing ideas, and by preparing model materials for study for physicists and pharmacologists in the group. In this way, they will derive multi-disciplinary research findings related to their materials and will also contribute to a research infrastructure whereby the physicists and pharmacologists will be able to conduct careful studies on well-defined macromolecules and macromolecular-magnetic particle complexes.